title: Tumor necrosis factor alpha promoter polymorphism and severity of acute kidney injury.
abstract: BACKGROUND
  Tumor necrosis factor-alpha is a proinflammatory cytokine that has been implicated in the pathobiology of acute kidney injury (AKI).
  
  
  METHODS
  We explored the association of a functional polymorphism in the promoter region (rs1800629) of the TNFA gene with severity of AKI, as defined by level of glomerular filtration (serum cystatin C and creatinine) and tubular injury (urinary NAG, KIM-1, α-GST, and π-GST) markers, in 262 hospitalized adults.
  
  
  RESULTS
  In unadjusted analyses, compared with the GG genotype, the TNFA GA and AA genotype groups tended to have higher enrollment (p = 0.08), peak (p = 0.004), and discharge (p = 0.004) serum creatinine levels, and the AA genotype tended to have a higher enrollment serum cystatin C level (p = 0.04). Compared with the GG genotype, the TNFA GA and AA genotype groups tended to have a higher urinary KIM-1 level (p = 0.03), and the AA genotype group tended to have a higher urinary π-GST level (p = 0.03). After adjustment for sex, race, age, baseline estimated glomerular filtration rate, sepsis, and dialysis requirement, compared with the GG genotype, the TNFA minor A-allele group had a higher peak serum creatinine of 1.03 mg/dl (0.43, 1.63; p = 0.001) and a higher urinary KIM-1 (relative ratio: 1.73; 95% CI: 1.16, 2.59; p = 0.008). The TNFA minor A-allele group also had a higher Multiple Organ Failure score of 0.26 (95% CI: 0.03, 0.49; p = 0.024) after adjustment for sex, race, age, and sepsis.
  
  
  CONCLUSIONS
  The TNFA rs1800629 gene polymorphism is associated with markers of kidney disease severity and distant organ dysfunction among patients with AKI. Larger studies are needed to confirm these relationships.
authors.affiliation: Department of Medicine, Division of Nephrology, Kidney and Dialysis Research Laboratory, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass., USA.
authors.forename: Paweena
authors.initials: P
authors.lastname: Susantitaphong
authors.forename: Mary C
authors.initials: MC
authors.lastname: Perianayagam
authors.forename: Hocine
authors.initials: H
authors.lastname: Tighiouart
authors.forename: Orfeas
authors.initials: O
authors.lastname: Liangos
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
authors.forename: Bertrand L
authors.initials: BL
authors.lastname: Jaber
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D000368:Aged; D001900:Boston / Q000453:epidemiology; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha